Administration of low dose triclosan to pregnant ewes results in placental uptake and reduced estradiol sulfotransferase activity in fetal liver and placenta.
Administration of low dose triclosan to pregnant ewes results in placental uptake and reduced estradiol sulfotransferase activity in fetal liver and placenta.
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DOI：
10.1016/j.toxlet.2018.05.014
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发表时间：
2018-09-15
影响因子：
3.5
通讯作者：
Wood CE
中科院分区：
文献类型：
--
作者：
Jackson EN;Rowland-Faux L;James MO;Wood CE
磺化是雌激素生物转化的主要途径，在调节人和羊体内雌激素的稳态中起作用。先前的体外研究发现，三氯生是绵羊胎盘雌激素磺基转移酶的一种特别有效的竞争性抑制剂，Kic <0.1 nM。由于胎盘是女性和绵羊妊娠期雌激素合成的主要器官，肝脏是雌激素生物转化的另一个部位，因此本研究检查了三氯生暴露对妊娠母羊胎盘和肝脏磺基转移酶活性的影响。通过直接输注到胎羊循环或输注到母体血液中，对妊娠晚期胎羊给予三氯生（0.1 mg/kg/天）或生理盐水溶剂，持续2天。在第三天，收获胎肝和胎盘并分析三氯生和细胞溶质雌二醇磺基转移酶活性。在两个治疗组中，每只绵羊胎盘中三氯生的浓度高于肝脏。三氯生组织浓度（pmol/g组织）和细胞溶质磺基转移酶活性（pmol/min/mg蛋白）对雌二醇呈负相关。这些发现表明，在暴露于极低浓度三氯生的绵羊中，该物质被吸收到胎盘中并降低雌激素磺化作用。
Sulfonation is a major pathway of estrogen biotransformation with a role in regulating estrogen homeostasis in humans and sheep. Previous in vitro studies found that triclosan is an especially potent competitive inhibitor of ovine placental estrogen sulfotransferase, with Kic of <0.1 nM. As the placenta is the main organ responsible for estrogen synthesis in pregnancy in both women and sheep, and the liver is another site of estrogen biotransformation, this study examined the effects of triclosan exposure of pregnant ewes on placental and hepatic sulfotransferase activity. Triclosan, 0.1 mg/kg/day, or saline vehicle was administered to late gestation fetal sheep for two days either by direct infusion into the fetal circulation or infusion into the maternal blood. On the third day, fetal liver and placenta were harvested and analyzed for triclosan and for cytosolic estradiol sulfotransferase activity. Placenta contained higher concentrations of triclosan than liver in each individual sheep in both treatment groups. There was a negative correlation between triclosan tissue concentration (pmol/g tissue) and cytosolic sulfotransferase activity (pmol/min/mg protein) towards estradiol. These findings demonstrated that in the sheep exposed to very low concentrations of triclosan, this substance is taken up into placenta and reduces estrogen sulfonation.
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